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A comparison of copper(I) and silver(I) complexes of glycine, diglycine and triglycine Tamer Shoeib, Christopher F. Rodriquez, K. W. Michael Siu and Alan C. Hopkinson* Department of Chemistry and Center for Research in Mass Spectrometry, Y ork University, 4700 Keele Street, T oronto, Ontario, Canada M3J 1P3. E-mail : ach=yorku.ca Received 2nd November 2000, Accepted 8th January 2001 First published as an Advance Article on the web 7th February 2001 Density functional calculations at B3LYP/DZVP were used to obtain structural information, relative free energies of di†erent isomers and binding energies for the following reaction in the gas phase : M` ] (glycyl) glycine ] MÈ(glycyl) glycine`, where M \ Ag or Cu and n \ 0È2. For the complexes with Cu`, n n optimizations were also performed at B3LYP/6È31&&G(d,p) and single-point calculations at MP2(fc)/6È311&&G(2df,2p)//B3LYP/DZVP. The calculated binding energies for the Cu` complexes are all higher than those of the structurally similar Ag` ions. These calculated binding energy di†erences become larger as the size of the ligand increases. For all the Cu` complexes examined, the coordination number of the copper ion does not exceed two, whereas for the silver complexes tri- and tetracoordinate Ag` structures are calculated to be at low energy minima. SigniÐcant structural and relative free energy di†erences occur between the lowest energy “ zwitterionic Ï forms of the MÈ(glycyl) glycine` complexes. n Introduction The area of gas-phase transition metal ion chemistry has experienced explosive growth in the recent past.1 This has been stimulated by the importance of transition metal ions in a wide variety of Ðelds, including catalysis, organometallic reactions and especially biochemistry, where metal ions can be very inÑuential in determining the three-dimensional structures of nucleic acids.2h5 For many proteins, a variety of metal ions are required to interact with the appropriate peptides or proteins in order for the latter to be able to carry out their regulatory or structural functions.6 It is therefore imperative that we further our understanding of the interactions of these metal ions with molecules of biological importance. Alkali metal cations, for example, are essential for maintaining osmotic equilibrium in cells ; they also play a role in the transport of amino acids through their binding to some proteins.7h9 Transition metal ions, such as Cu(I), also play very important roles in biological processes such as oxidation, dioxygen transport and electron transfer.7,10 Silver(I) compounds, on the other hand, are used as potent antibacterial agents.11 Excluding those of mercury, silver compounds are among the most toxic towards bacteria and other microorganisms. This fact is exploited by the use of silver(I) compounds for medicinal purposes ; silver nitrate has been used to combat infantile blindness12 and silver sulfadiazine is commonly found in creams used to treat severe burns and infectious skin diseases.13,14 The role of silver sulfadiazine has been examined and the general agreement is that the action of the drug is due to its ability to release silver ions which are the active species.14 Silver(I) diphosphine complexes have been shown to be potently cytotoxic to cancerous melanoma cells,15 while other silver-containing compounds have been e†ectively used for treatment of ulcers.16 Metal ions can bind to a variety of sites on a peptide, including the amino nitrogen at the N-terminus, the carboxylate anion at the C-terminus, the carbonyl oxygen atoms along the backbone and the side chains of the glutamine and DOI : 10.1039/b008836f asparagine residues, and the nitrogen atoms on the side chains of basic residues such as lysine, arginine and histidine. Other possible sites of metal ion attachment to peptides include the hydroxyl oxygen atoms on the side chains of serine, threonine and tyrosine residues and the sulfur atoms on the side chains of methionine and cysteine residues. The fact that a variety of metal ions can easily bind to peptides has been exploited in the Ðeld of mass spectrometry, where metal ions such as Li`, Na`, Cu` and Ag` have been used as ionizing agents for peptide sequencing.17h19 Exploring the nature of these metal ionÈpeptide interactions will not only provide information on their binding energies to a class of biologically important molecules, but will also be extremely useful in the interpretation of the mass spectra of such complexes obtained either under metastable or via collision-induced dissociation conditions. The coordination modes of metal ions greatly inÑuence their binding energies and to some extent their site of attachment to a ligand. Some metals have a strong preference for a particular coordination mode, while others can adopt di†erent coordination geometries. These coordination preferences could play a signiÐcant role in the biological functions of metal-containing enzymes. The metal-speciÐc binding sites of some proteins achieve their selectivity by providing a coordination environment preferred by only one metal ion naturally found in living systems. As a consequence, some metals that are not naturally found in living systems owe their toxicity to their ability to coordinate strongly and compete e†ectively for the binding sites of biologically important metal ions. Modeling ionÈprotein complexes is a difficult task that requires accurate knowledge of the interactions of these ions with amino acids and small peptides. Recently, the kinetic method has been used to obtain ladders of relative Cu` and Ag` affinities of almost all essential a-amino acids.20,21 Theoretical studies have also probed the interactions of Cu` with glycine, cysteine and serine 22,23 and those of Ag` with all 20 a-amino acids.24 While these studies provide values of the binding energies and some insight into the coordination preferences of these two isoelectronic transition metal ions, no Phys. Chem. Chem. Phys., 2001, 3, 853È861 This journal is ( The Owner Societies 2001 853 direct comparisons between their interactions with amino acids or peptides have previously been made. This work provides a step towards this goal by means of a comprehensive description of the interaction of Cu` and Ag` with each of glycine (G), glycylglycine (GG) and glycylglycylglycine (GGG). Glycine was chosen as several groups have studied its interaction with metal ions, including Cu`, and its binding energy to that ion is well established.22,23 For reasons of computational tractability, the largest peptide that is being examined is triglycine, the smallest peptide unit that reasonably models binding present in some larger peptides. Methods The most reliable theoretical value in the literature for the Cu` affinity of glycine was obtained by the CCSD(T) method with a very large basis set.23 Unfortunately, this level of theory is computationally prohibitive for calculations on peptides such as GG and GGG. The procedure used here was to perform structure optimization calculations using hybrid density functional theory at the B3LYP level25h27 using the DZVP basis set28 and to follow these by single-point calculations at MP2(fc)/6È311&&G(2df,2p).29h36 The latter level of theory has been shown to reproduce satisfactorily the Cu` binding energy of glycine as calculated by the CCSD(T) method.23 As an independent check on the geometries and energetics provided by this procedure, we also optimized three conformers of GGG and the three lowest isomers of GGGÈCu` at B3LYP/6È31&&G(d,p).37,38 In every comparison, we found no substantive di†erences in the structures and relative energies provided by the two di†erent basis sets. Ag` affinities were calculated at B3LYP/DZVP. This approach has been shown to provide excellent agreement with experimental values for systems similar to those under study here.39,40 All calculations were performed using the GAUSSIAN 98 program.41 All geometry optimizations were performed without any symmetry constraints and all optimized structures were characterized by harmonic frequency calculations and shown to be at minima. Results and discussion Structural details and relative free energies Glycine. Neutrals. The structure of neutral and metal ion containing glycine in the gas phase has been the subject of several extensive investigations.42h44 Only the three lowest energy conformers as previously determined were investigated here. These structures are shown in Fig. 1. Total energies, zero-point vibrational terms, thermal corrections, entropies and their relative free energies are given in Table 1. GlycineÈAg`. All attempts to optimize a tricoordinate Ag` structure by allowing for interactions of the metal ion with the nitrogen and each of the oxygen atoms of glycine eventually resulted in 1Ag, the lowest energy structure found (Fig. 1). 2Ag is the lowest energy structure of the “ zwitterionic ÏÏ form, the structure in which Ag` is added to the zwitterion of glycine. This is only 4.5 kcal mol~1 higher in free energy than 1Ag (see Table 1). GlycineÈCu`. Here, just as others have reported,22 attempts to produce a tricoordinate glycineÈCu` structure were not successful. The structural parameters for the lowest energy structure found for this complex, 1Cu, are shown in Fig. 1. Ion 1Cu is dicoordinate, with the two most basic sites of glycine, the terminal amino group and the carbonyl oxygen, interacting with Cu`. This structure is similar to that of 1Ag on the glycineÈAg` surface, although the metalÈligand distances Fig. 1 Structures of glycine and AgÈglycine` and CuÈglycine` complexes as optimized at B3LYP/DZVP. Upper numbers are for M \ Ag and lower italicized numbers are for M \ Cu. Bond lengths are in a- ngstroms and angles are in degrees. 854 Phys. Chem. Chem. Phys., 2001, 3, 853È861 Table 1 Total electronic energies, unscaled zero-point energies (ZPE), enthalpy corrections, entropies and relative free energies. Upper numbers are calculated at B3LYP/DZVP and lower bold face numbers are calculated at MP2(fc)/6È311&&G(2df,2p)//B3LYP/DZVP Structure 1N 2N 3N Ag` 1Ag 2Ag Cu` 1Cu 2Cu Electronic energy/hartree ZPE/ kcal mol~1 H¡ [ H¡/ 298mol~1 0 kcal Entropy/ cal mol~1 K~1 Relative free energy at 298 K/kcal mol~1 [284.477 42 Ô283.938 99 [284.475 10 Ô283.936 39 [284.476 33 Ô283.938 23 [5199.198 15 [5483.759 22 [5483.751 50 [1639.887 04 Ô1639.050 19 [1924.491 38 Ô1923.102 27 [1924.475 86 Ô1923.086 80 50.1 4.1 75.2 50.2 4.1 76.0 50.5 3.9 73.4 0.0 0.0 1.3 1.9 1.4 4.0 51.8 51.8 1.5 5.0 5.2 1.5 39.9 86.5 88.3 38.4 52.1 4.9 84.2 52.1 5.1 86.9 are shorter in the glycineÈCu` complex. This is simply a reÑection of the smaller ionic radius of Cu`. Structure 2Cu is the lowest energy conformer of the zwitterionic form of the complex ; it lies 9.2 kcal mol~1 higher in free energy than 1Cu. This relative free energy di†erence is more than double the free energy di†erence of the equivalent glycineÈAg` structures. This could be explained by considering the fact that, unlike Ag` in structure 2Ag, Cu` in structure 2Cu coordinates only with one of the oxygen atoms of the CO ~ group. This unsymmetrical coordination of the lowest 2 energy zwitterionic form of the glycineÈCu` complex was previously reported22,23 and was attributed to the strong local dipoles on the NÈH bonds that lead to a global dipole moment pointing towards the opposite oxygen.22 However, it has been pointed out that the analogous M`ÈCO ~ coordi2 nation with alkali metal cations (e.g., Li`, Na`, K`, Rb` and Cs`) all show dicoordination despite similar dipole moment e†ects.23,44 An alternative explanation is that the unsymmetrical interactions of Cu` to the CO ~ group of the zwitterionic 2 form of glycine provide a way of minimizing the repulsion between the occupied d shell of the metal and the lone pairs of oxygens.23 This argument, however, is also unsatisfactory as Ag` is isoelectronic with Cu` and yet prefers symmetrical coordination with the CO ~ group of the zwitterionic form of 2 glycine. In both cases, however, the presence of the metal ion strongly stabilizes the zwitterionic form of glycine ; on the potential energy hypersurface for glycine the zwitterion is not even at a minimum.45 Glycylglycine. Neutrals. Conformational searches using molecular mechanics techniques were used to investigate rapidly the potential energy surface of neutral GG. The lowlying conformers obtained from this search were then optimized at B3LYP/DZVP, followed by single-point calculations at MP2(fc)/6È311&&G(2df,2p) (see Fig. 2 and Table 2). The three lowest energy structures obtained for this surface are shown in Fig. 2. Two of these three structures, 4N and 5N, have folded conformations. Recently, Cerda et al.46 reported structure 4N to be the lowest energy conformer on this surface ; however, in their work structure 5N was not considered. As shown in Fig. 2, structure 5N, displaying two internal hydrogen bonds, appears to be the most compact of the three conformers. These three conformers have almost identical free energies, and therefore it is important to clarify that for our discussion of signiÐcant structural and relative free energy di†erences of complexes of Cu` and Ag` with 0.0 4.5 0.0 0.0 9.2 9.2 polyglycines and also for providing good estimates of the binding energies of these two metal ions, it is not crucial that the global minimum of the neutral peptide be identiÐed. GlycylglycineÈAg`. Previously we have shown 47 that the ““ external ÏÏ proton in protonated triglycine is ““ mobile ÏÏ. In that study47 we demonstrated that the barriers involved for the ““ external ÏÏ proton to migrate from the terminal nitrogen to any of the carbonyl oxygen atoms along the peptide backbone are relatively low. In a subsequent study, we also showed that these barriers are signiÐcantly lowered by the addition of a single solvent molecule.48 Based on this knowledge, we did not limit ourselves in this study to structures where the proton is on the terminal amino group. The potential energy surface of the GGÈAg` complex was rigorously examined. Eleven structures on this surface were optimized and characterized as being at minima. The lowest energy structure, 3Ag, found on this surface is shown in Fig. 2. This structure is very similar to the lowest energy structure of the glycineÈAg` complex, ion 1Ag, where the silver ion is dicoordinate, attached to the terminal nitrogen and the carbonyl oxygen of the amide. Structure 4Ag, depicts the only tricoordinate silver complex of GG found on this surface ; here the silver ion is chelated to the terminal nitrogen and to both of the carbonyl oxygens of GG. Interaction of Ag` with the three most electron-rich sites of GG might a priori be expected to lead to the lowest energy structure ; however, the steric e†ect of folding the GG backbone to accommodate this mode of coordination makes this structure less favored, but still competitive at a relative free energy of only 1.2 kcal mol~1 higher than the structure at the global minimum. Ion 5Ag, where Ag` binds to both carbonyl oxygen atoms, is further stabilized by a hydrogen bond in which the lone pair on the terminal amino interacts with an amide hydrogen that has been rendered more acidic by complexation of the oxygen on the same amide linkage with Ag`. This ion is found to be at a low-lying energy minimum, being only 2.5 kcal mol~1 above the global minimum. Permitting the silver ion to bind with both the terminal amino nitrogen and the terminal carbonyl oxygen results in isomer 6Ag, a structure that is 6.6 kcal mol~1 higher in energy than 3Ag. The zwitterionic forms of the GGÈAg` complex were also extensively investigated. The three lowest energy conformers of this form of the ion are shown in Fig. 2. The lowest energy structure of all the zwitterions on this surface, structure 7Ag, is only 8 kcal mol~1 above structure 3Ag. This zwitterionic structure is stabilized by two internal hydrogen bonds. One of these bonds is between the terminal amino nitrogen and the acidic amide hydrogen ; the second, and signiÐcantly stronger Phys. Chem. Chem. Phys., 2001, 3, 853È861 855 Fig. 2 Structures of diglycine and AgÈdiglycine` and CuÈdiglycine` complexes as optimized at B3LYP/DZVP. Upper numbers are for M \ Ag and lower italicized numbers are for M \ Cu. Bond lengths are in a- ngstroms and angles are in degrees. interaction, is between the hydroxy hydrogen and the carbonyl oxygen of the CO ~ group. The latter interaction is by far 2 the shortest hydrogen bond found on this potential hypersurface. The position of the hydrogen atom between two very electronegative sites, the relatively short distance between that hydrogen and the carbonyl oxygen of the CO ~ group (1.399 2 856 Phys. Chem. Chem. Phys., 2001, 3, 853È861 A ) and the OÈHÈO angle of 174¡, which is nearly the ideal 180¡, are all factors that contribute to the strength of this hydrogen bond and hence to the stability of this structure. The other two zwitterionic structures presented here, 8Ag and 9Ag, both involve the localization of some of the positive charge on the terminal nitrogen ; this arrangement leads to Table 2 Total electronic energies, unscaled zero-point energies (ZPE), thermal energies, entropies and relative free energies. Upper numbers are calculated at B3LYP/DZVP, central italicized numbers are calculated at B3LYP/6È31&&G(d,p) and lower bold face numbers are calculated at MP2(fc)/6È311&&G(2df,2p)//B3LYP/DZVP Structure 4N 5N 6N 3Ag 4Ag 5Ag 6Ag 7Ag 8Ag 9Ag 3Cu 5Cu 6Cu 7Cu 8Cu 9Cu Electronic energy/ hartree [492.518 12 Ô491.572 24 [492.519 88 Ô491.575 51 [492.516 19 Ô491.570 98 [5691.814 03 [5691.811 73 [5691.808 48 [5691.803 59 [5691.801 24 [5691.795 27 [5691.793 79 [2132.549 45 [2132.637 91 Ô2130.752 37 [2132.545 94 [2132.634 36 Ô2130.747 07 [2132.550 17 [2132.636 80 Ô2130.753 68 [2132.525 74 Ô2130.728 21 [2132.523 11 Ô2130.726 23 [2132.521 26 Ô2130.724 12 ZPE/ kcal mol~1 H¡ [ H¡/ 298 0 kcal mol~1 Entropy/ cal mol~1 K~1 85.4 6.7 100.7 85.8 6.5 95.6 85.0 6.9 100.5 86.9 86.7 86.4 87.0 85.4 87.6 86.7 87.3 87.1 7.7 7.7 7.9 7.1 7.7 7.5 7.8 7.5 6.9 109.8 109.2 111.3 109.9 111.3 108.3 111.7 107.4 106.5 86.9 86.8 7.5 6.9 105.5 105.1 87.8 87.7 7.2 6.6 103.1 102.3 86.0 7.6 109.5 88.1 7.3 105.3 86.9 7.7 109.3 some charge separation, as the metal center and the terminal NH ` group account for most of the positive charge in these 3 species. GlycylglycineÈCu`. All attempts to form tricoordinate structures of Cu` failed. Structure 3Cu, where Cu` is chelated to the terminal amino group and the carbonyl oxygen of the amide, is at the global minimum structure on this surface. However, in contrast to the GGÈAg` potential energy surface, structure 6Cu, in which the two terminal groups chelate Cu`, is almost degenerate with the global minimum. As on the GGÈAg` surface, structure 5, where the Cu` coordinates with both of the carbonyl oxygens of GG, is a relatively low energy species, only 2.4 kcal mol~1 higher in free energy relative to the global minimum. The zwitterionic forms of the GGÈCu` complex display remarkable di†erences from those of their Ag` counterparts, both in structure and free energies relative to their respective global minima. Cu` clearly displays its preference for monocoordination to only one of the oxygen atoms of the CO ~ 2 group in structure 7Cu. The presence of the two intramolecular hydrogen bonds in this structure, similar to those in 7Ag, the GGÈAg` counterpart of this structure, help to stabilize this isomer. However, the preference of Cu` for monocoordination makes this structure a relatively high energy species, 12.5 kcal mol~1 higher in free energy above 3Cu. The preference of Cu` to be monocoordinate with the CO ~ group of the zwitterionic form of GG is also shown in 2 structure 8Cu. Despite the stabilizing e†ect of the hydrogen bond between the terminal ammonium group and the carbonyl of the C-terminus, this structure is not energetically favorable relative to others on this surface. Structure 9Cu, the highest energy species of GGÈCu` considered in this work, is interesting as, unlike in 7Cu and 8Cu, it has the Cu` dicoordinated with both oxygens of the CO ~ 2 group in a nearly symmetrical fashion. This is perhaps due to the absence of strong intramolecular hydrogen bonding interactions with either of these oxygens. Such interactions deplete Relative free energy at 298 K/ kcal mol~1 0.0 0.4 0.5 0.0 0.5 1.3 0.0 1.2 2.5 6.6 6.2 12.8 13.1 0.0 0.0 0.0 2.4 1.5 3.5 1.0 2.9 0.6 12.5 13.2 17.4 17.6 16.9 17.0 some of the electron density from the carbonyl oxygen where the hydrogen bonding takes place, thereby rendering that carbonyl oxygen a less attractive binding site for the copper ion. This seems to be a more satisfactory explanation of the unsymmetrical coordination of Cu` to the CO ~ group of the 2 zwitterions encountered here and previously in the literature.22,23 Further evidence is obtained upon careful inspection of structure 9Cu. The weak hydrogen bond between the mildly acidic amide hydrogen and the adjacent carbonyl oxygen of the CO ~ group causes some depletion of some of 2 the electron density on that oxygen, thereby rendering it a less attractive site for Cu` attachment, as reÑected in the longer bond distance between that oxygen and the metal center (2.185 A ) relative to the of the metal center and the other carbonyl oxygen of the CO ~ group (2.067 A ). This explanation 2 is further corroborated with the symmetrical coordination observed in this work of Cu` to the carbonyl oxygens of the CO ~ group of cuprous formate, a molecule devoid of any 2 hydrogen bonding. Glycylglycylglycine. Neutrals. Various conformers of GGG were previously examined by Zhang et al.,49 and also more recently by Strittmatter and Williams50 in their attempts to obtain accurate values for the proton affinity of GGG. While the proton affinities obtained by both groups are comparable and agree well with experimental values,51 the level of theory used in their work is modest by todayÏs standards. The potential energy surface of neutral GGG has been shown to be relatively Ñat with many structures at low energy minima. We have performed independent conformational searches and optimized many of the lowest energy conformers at B3LYP/ DZVP (see Table 3 and Fig. 3. The HF/6È31G(d) results of Zhang et al.49 were taken as starting points in our optimization work. The three lowest energy conformers found were virtually degenerate and hence, in our endeavor to identify the lowest energy isomer of neutral GGG, all three isomers considered here were reoptimized with a basis set Phys. Chem. Chem. Phys., 2001, 3, 853È861 857 including di†use functions [at B3LYP/6È31&&G(d,p)]. This reconÐrmed that every one of the three structures is at a minimum, while producing a relative free energy spread of only 0.2 kcal mol~1. Single-point calculations on all three isomers were performed at MP2(fc)6È311&&G(2df,2p) using the optimized geometry of B3LYP/DZVP. The results of these calculations indicate that 8N and 9N are virtually degenerate with 9N being favored by only 0.4 kcal mol~1, while 7N is 2.5 kcal mol~1 higher in energy than 9N. This relative order is probably due to the better description of the intramolecular hydrogen bonds found in both 8N and 9N by the inclusion of di†use and extra polarization functions in the larger basis set used in our MÔllerÈPlesset perturbation (MP2) calculations. While we do not claim to have deÐnitively identiÐed the structure at the global minimum on the neutral GGG surface, we have shown that 8N and 9N are essentially degenerate independent of the level of theory and that it is inconsequential to our study which of these three isomers is used for binding energy determination. Glycylglycylglycine-Ag`. Much as in the GGÈAg` complexes, the silver(I) ion demonstrates its ability to act as a multicoordinate center in GGG-Ag`. The global minimum found for this surface, structure 10Ag, has a tetracoordinate Ag` having interactions with the terminal amino group as well as each of the three carbonyl oxygens of GGG. In order to allow for this mode of coordination around the central metal center, the backbone of this tripeptide must undergo a signiÐcant distortion. The energy cost of this steric requirement is more than compensated by the interactions of Ag` with the four most electron rich sites of GGG. This is evident upon comparison of structure 10Ag with structure 14Ag where the silver ion is chelated only to the terminal nitrogen and the adjacent carbonyl oxygen. While this mode of coordination allows for a less sterically hindered GGG backbone, structure 14Ag is calculated to be 3.2 kcal mol~1 higher in energy than 10Ag ; this highlights the energetic importance of the secondary interactions of the Ag` with the carbonyl groups of the second residue and of the carboxylic acid group. In the dipeptide case, structure 4Ag, which is the analogous structure of 10Ag on the GGGÈAg` surface, was found to be higher in energy than 3Ag, the comparable structure to 10Ag. This is perhaps indicative of the extra stabilization a†orded by the fourth silverÈligand bond in 10Ag as well as the relatively higher steric cost associated with folding the shorter GG backbone in order to allow for the geometry needed for a tricoordinate Ag`. Structure 12Ag is another conformer that displays the ability of Ag` to become a multicoordinate center. Here the silver ion is simultaneously chelated to all three carbonyl oxygens in GGG. This isomer is nearly degenerate with the lowest energy isomer 10Ag. Structures 15Ag and 16Ag shown in Fig. 3 both feature a dicoordinate Ag` and are both about 10 kcal mol~1 higher in free energy relative to 10Ag. The zwitterionic species 17Ag and 19Ag are the highest energy forms of the GGG-Ag` complex investigated in this work and are 18.9 and 19.6 kcal mol~1, higher in free energy relative to 10Ag. GlycylglycylglycineÈCu`. All structures investigated were found to be dicoordinate with respect to the copper ion ; no structure with higher coordination at Cu` was found to be at a minimum. The geometry of structure 11Cu, where the Cu` is coordinated to the carbonyl oxygens on the terminal residues, is such that an angle close to the ideal 180¡ is a†orded between the metal and the ligands. This favorable coordi- Table 3 Total electronic energies, unscaled zero-point energies (ZPE), enthalpy corrections, entropies and relative free energies. Upper numbers are calculated at B3LYP/DZVP, central italicized numbers are calculated at B3LYP/6È31&&G(d,p) and lower bold face numbers are calculated at MP2(fc)/6È311&&G(2df,2p)//B3LYP/DZVP Structure 7N 8N 9N 10Ag 12Ag 14Ag 15Ag 16Ag 17Ag 19Ag 11Cu 13Cu 14Cu 15Cu 16Cu 18Cu 19Cu 858 Electronic energy/ hartree [700.560 76 [700.510 79 Ô699.207 03 [700.564 44 [700.515 23 Ô699.214 21 [700.565 46 [700.515 46 Ô699.216 78 [5899.873 32 [5899.868 94 [5899.861 70 [5899.855 06 [5899.854 85 [5899.838 23 [5899.838 23 [2340.619 80 [2340.693 56 Ô2338.417 04 [2340.622 14 [2340.693 79 Ô2338.421 87 [2340.598 06 Ô2338.393 31 [2340.612 86 [2340.685 26 Ô2338.411 74 [2340.592 72 Ô2338.388 13 [2340.562 63 Ô2388.360 68 [2340.567 34 Ô2338.361 92 ZPE/ kcal mol~1 H¡ [ H¡/ 298mol~1 0 kcal Entropy/ cal mol~1 K~1 119.8 119.5 9.8 9.8 128.5 129.1 120.8 120.5 9.3 9.3 122.1 122.5 121.1 120.6 9.1 9.2 118.6 121.6 122.1 121.3 121.8 122.3 121.8 120.2 121.7 121.9 121.9 10.3 10.6 10.5 10.3 10.4 10.4 10.5 10.2 10.1 128.4 132.8 135.2 134.1 131.7 133.0 135.8 126.7 125.0 123.2 123.1 9.8 9.8 124.1 124.4 122.1 10.3 131.7 122.8 122.7 9.9 9.9 126.7 126.1 122.1 10.1 127.4 120.7 10.3 130.7 121.8 10.5 134.4 Phys. Chem. Chem. Phys., 2001, 3, 853È861 Relative free energy at 298 K/ kcal mol~1 0.0 0.2 2.5 0.1 0.1 0.4 0.7 0.0 0.0 0.0 0.9 3.2 10.0 10.4 18.9 19.6 0.0 1.3 1.4 0.2 0.0 0.0 14.6 15.1 5.0 4.6 5.4 19.1 19.4 33.6 33.8 30.8 33.8 Fig. 3 Structures of triglycine and AgÈtriglycine` and CuÈtriglycine` complexes as optimized at B3LYP/DZVP. Upper numbers are for M \ Ag and bottom italicized numbers are for M \ Cu. Bond lengths are in a- ngstroms and angles are in degrees. nation angle is also present in structure 13Cu, where the coordination sites are the terminal carbonyl and the terminal amino group. This favorable coordination angle may play a role in that these isomers are nearly degenerate in free energy. Structures 15Cu, 14Cu and 16Cu are less energetically favored, being 5.0, 14.6 and 19.1 kcal mol~1, respectively, higher in free energy than 11Cu. The zwitterionic structure 18Cu is yet another example of Phys. Chem. Chem. Phys., 2001, 3, 853È861 859 Table 4 Binding energies for ions ML` calculated at B3LYP/DZVP. Bold face values are calculated at MP2(fc)/6È311&&G(2df,2p)// B3LYP/DZVP. Italicized values are reported at 0 K DH¡ /kcal mol~1 298 Species L NH 3 H CO 2 H NCHO 2 Glycine (G) GG GGG M \ Ag` M \ Cu` 40.1 28.5 39.6 48.1 57.9 64.6 49.0a, 49b, 52.2c, 51.8d, 52.3e 42.1, 36.8c 56.9, 56.2c, 52.6c 70.5, 68.6, 68.1f 80.4, 80.3 95.2, 94.8 a Ref. 54. b Ref. 55. c Ref. 56. d Ref. 57. e Ref. 58. f Ref. 23. the unsymmetrical coordination of Cu` to the CO ~ group in 2 the presence of a hydrogen bond to one of the oxygens in the CO ~ group. This monocoordination of the metal might be 2 among the reasons for structure 18Cu to have the highest energy encountered on this surface. Structure 19Cu is another zwitterionic form of the GGG-Cu` complex ; this structure is similar to 9Cu on the GG-Cu` surface, in that both of these ions have the metal center coordinating with both of the oxygen atoms of the CO ~ group in a nearly symmetrical 2 fashion. Binding energies The binding energies of Ag` and Cu` to glycine, diglycine and triglycine and to some small molecules that contain the functional groups present in peptides are presented in Table 4, all corrected for basis set superposition errors (BSSE) by using the counterpoise method.52,53 At this level of theory the corrections are typically 2È3 kcal mol~1. The binding energies of all Cu` containing ions considered here are greater than those of their Ag` analogs. The ligand for which the di†erence in the binding energies in complexes with the two metal ions is smallest is NH , the simplest model of the terminal amino 3 group present in a peptide. The di†erence of the binding energies in complexes with H CO, the simplest carbonyl2 containing molecule, is about 14 kcal mol~1. The di†erence of 17 kcal mol~1 for H NCHO is larger still ; this is the simplest 2 model that contains both a terminal amino nitrogen and a carbonyl functionality. This divergence increases even when the binding energies to each of glycine, diglycine and triglycine are considered ; here the di†erences are 20.6, 22.4 and 30.2 kcal mol~1 respectively. To the best of our knowledge, the silver ion affinities presented here are the Ðrst values of *H¡ in the literature. The 298 Cu`Èglycine complex has been the subject of previous investigations and the most accurate calculated binding energy available is presented in Table 4. This value of 68.1 kcal mol~1 obtained from CCSD(T) calculations is well reproduced by the less computationally demanding approach adopted here (see Table 4). Conclusions In all the ML` complexes investigated, the highest coordination number observed for Cu` was found to be two. By contrast, Ag` does form tri- and tetracoordinate structures. When Ag` adopts higher coordination, tricoordinate in the case of diglycine and tri- and tetracoordinate in the case of triglycine, these structures in all instances were found to be at low energy minima. Several groups have shown dicoordinate Cu` complexes always to adopt a linear geometry in the gas phase. This could be one of the reasons behind the stability of the two lowest energy structures of the GGGÈCu` complex, where the angle comprising the two coordinating sites and the metal is nearly the ideal 180¡. 860 Phys. Chem. Chem. Phys., 2001, 3, 853È861 The binding energies for all the Cu` complexes are all larger than those of the analogous Ag` species. The di†erence is found to increase as the size of the ligand increases. 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